PATIENT BASELINE CHARACTERISTICS IN THE ONGOING PHASE 3 VISIONARY TRIAL: A RANDOMIZED, PLACEBO-CONTROLLED STUDY OF SIBEPRENLIMAB FOR IMMUNOGLOBULIN A NEPHROPATHY

Introduction:

Immunoglobulin A nephropathy (IgAN), clinically characterized by proteinuria and a progressive decline in kidney function, is the most common primary glomerulonephritis worldwide. The annual global incidence of IgAN is 2.5 cases per 100,000 persons; however, this varies by region and ethnicity (McGrogan, et al. Nephrol Dial Transplant. 2011). A PRoliferation-Inducing Ligand (APRIL) plays a key role in the immune-related pathogenesis of IgAN. In the recently completed Phase 2 ENVISION trial, sibeprenlimab (an anti-APRIL humanized immunoglobulin G2 monoclonal antibody) demonstrated significant reduction in proteinuria and stabilization of estimated glomerular filtration rate (eGFR), with a favorable safety profile in patients with IgAN (Mathur, et al. NEJM. 2024). Here we report the baseline clinical characteristics of patients enrolled in the VISIONARY trial, a Phase 3 study of sibeprenlimab administered subcutaneously (SC) in adult patients with IgAN (NCT05248646).
 

Methods:

VISIONARY is an ongoing, multicenter, double-blind, placebo-controlled trial designed to evaluate the efficacy and safety of sibeprenlimab SC in patients with IgAN. Patients who were on a stable and maximally tolerated renin-angiotensin system (RAS) blockade, with or without sodium-glucose cotransporter-2 inhibitor (SGLT2i) background therapy, were randomized 1:1 to receive sibeprenlimab 400 mg or placebo administered SC once every 4 weeks for 26 doses. Key inclusion and exclusion criteria are shown in Table 1. The primary efficacy endpoint is the relative change from baseline in the urinary protein to creatinine ratio (uPCR) in 24-hour urine collections, after 9 months of treatment. Demographic and baseline characteristics were summarized using descriptive statistics.

Results:

Of the 510 patients randomized, median age was 42 years (range, 18–83 years), and 59% were male. The majority of patients were Asian (59%) or White (37%); 1% were Black or African American, and <1% were American Indian or Alaska Native (Table 2). Patients were recruited across 5 continents: North America, South America, Europe, Asia, and Australia. At baseline, the mean uPCR-24h (standard deviation) was 1.5 g/g (0.9), with 21.4% of patients having a uPCR-24h >2.0 g/g at screening. At baseline, median eGFR was 60.0 mL/min/1.73m^2 (range, 25.0–134.0 mL/min/1.73m^2), and the median urine protein excretion at baseline was 1.8 g/day (range, <0.1–9.0 g/day). RAS blockade and SGLT2i use were reported in 97.8% and 45.1% of patients, respectively.

Conclusions:

The ongoing VISIONARY trial evaluating sibeprenlimab SC has recruited patients globally with IgAN who are at high risk of disease progression. Similar to the Phase 2 ENVISION study, diverse enrollment in this trial is representative of a broad population with high-risk disease and allows for evaluation of sibeprenlimab treatment across a spectrum of patients with IgAN. This trial will report clinical results at a future date.

I have potential conflict of interest to disclose.
The study and development of this abstract were funded by Otsuka.

I did not use generative AI and AI-assisted technologies in the writing process.